(PSI), in collaboration with clinicians at University of Pittsburgh Medical Center (UPMC) Eye Center and a consultant from Massachusetts Institute of Technology (MIT), propose to develop a novel compact multimode adaptive optics (AO) retinal imaging system to study the characteristics of age-related macular degeneration (AMD). The system will integrate AO, swept-source based Fourier domain optical coherence tomography (FDOCT), and scanning laser ophthalmoscopy (SLO). It will also include many clinical enhancements including retinal tracking for stabilized imaging. The system will sequentially acquire co-registered en-face scanning laser ophthalmoscopy (SLO) and cross- sectional OCT images of retinal cells and structures. In Phase I, we will design and construct the optical core including AO and swept source components. In Phase II, we will complete the prototype clinical instrument and test on human subjects with AMD at UPMC. We will explore the fine structure and margins of drusen in relation to photoreceptors, assess Bruch's membrane for discontinuity, and examine other sensitive adjacent structures in the retina during initiation and progression of the disease. The proposed system has the potential to resolve retinal details in the live eye at the very earliest stages of disease formation. This will provide information for full understand of the etiology and mechanisms of AMD, lead to methodologies for early detection, and help determine the efficacy of new genetic and molecular therapies. PUBLIC HEALTH RELEVANCE: By making high-resolution ocular access more widespread, the proposed instrument will begin to bring adaptive optics technology to a greater number of clinicians and scientists. These researchers will, in turn, use this tool to increase our understanding of vision and its disruption by diseases such as age-related macular degeneration and for the development of new drugs and therapies.